EGLN2 attenuates ovarian cancer malignancy via ferroptosis activation.

Growing evidence indicates that ferroptosis is pivotal in the development and progression of ovarian cancer (OC). However, the function of EGLN2 in OC remains unclear. In this study, we observed that EGLN2 is expressed at low levels in OC tissues and is associated with a favorable prognosis in early-stage patients based on data from TCGA and GTEx public databases. Compared with those in normal ovarian epithelial cell lines, EGLN2 mRNA and protein levels were significantly lower in OC cell lines. In vitro functional experiments revealed that EGLN2 overexpression reduced proliferation, increased the intracellular levels of iron ions, reactive oxygen species, lipid peroxidation, and mitochondrial oxidative phosphorylation, and inhibited the Warburg effect. Mechanistically, EGLN2 inhibited the expression of HIF-1α, which binds to the promoter of ceruloplasmin (CP), reducing the proliferation of and inducing ferroptosis in OC cells. A subcutaneous xenograft model in nude mice demonstrated that EGLN2 overexpression inhibited HIF-1α, promoted ferroptosis, and inhibited OC cell growth. In summary, EGLN2 suppressed CP transcription and increased ferroptosis in OC cells. These findings provide new insights into OC development and open avenues for innovative therapies.